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Densen Hayashi, Dayu Li, Chisato Hayashi, Marie Shatos, Robin R. Hodges, Darlene A. Dartt; Role of Histamine and Its Receptor Subtypes in Stimulation of Conjunctival Goblet Cell Secretion. Invest. Ophthalmol. Vis. Sci. 2012;53(6):2993-3003. doi: 10.1167/iovs.11-8748.
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The purpose of this study was to determine the effect of histamine and its receptors on goblet cell secretion.
Cultured rat and human goblet cells were grown in RPMI 1640. Goblet cell secretion of high molecular weight glycoconjugate was measured by an enzyme-linked lectin assay. Cultured rat goblet cells were homogenized and either RNA was isolated for RT-PCR or proteins were isolated for Western blot analysis for presence of histamine receptors subtypes H1 through H4. The localization of these receptors was determined in rat and human goblet cells by immunofluorescence microscopy.
Histamine stimulated goblet cell secretion in a concentration- and time-dependent manner. All four histamine receptors were present in cultured rat and human goblet cells. Use of agonists specific to individual histamine receptor subtypes indicated that the rank order of agonist stimulation was H1 = H3 > H4 > H2. Using antagonists specific to individual histamine receptor subtypes determined that H2 and H3, but not the H1 and H4, antagonists, inhibited histamine-stimulated conjunctival goblet cell secretion.
Rat and human conjunctival goblet cells are a direct target of histamine, which induces secretion. All four histamine receptors are present in rat and human conjunctiva and are active in rat conjunctival goblet cells. These findings suggest that all four histamine receptor subtypes are important for conjunctival goblet cell secretion. Blockage of histamine receptor subtypes could prevent the excess mucus production associated with ocular allergy.
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